Entry Detail
| General information | |
| Database: | DB00841 |
| Objective: | Everolimus, an oral inhibitor of mammalian target of rapamycin, can augment the efficacy of HER inhibitors in preclinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus and to describe its antitumor activity in the phase I setting. |
| Authors: | Gadgeel SM, et al |
| Title: | Phase I study evaluating the combination of lapatinib (a human epidermal growth factor receptor 2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528. |
| Journal: | Cancer Chemother Pharmacol. |
| Year: | 2013 |
| PMID: | 24057042 |
| Trial Design | |
| Clinical Trial Id: | NCT00352443 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced cancers |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lapatinib (a human epidermal growth factor receptor 2/Neu + EGFR inhibitor) + everolimus (an mTOR inhibitor) |
| Study Type: | Phase I study |
| Key Patients Feature: | patients with advanced cancers |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed. In Part II, PK of both drugs were analyzed to assess drugdrug interaction. |
| Primary End Point: | safety and pharmacokinetics (PK) |
| Secondary End Point: | NA |
| Patients Number: | 23 |
| Trial Results | |
| DLT_MTD: | Drug related toxicities were considered DLTs if patients developed one of the following during the first cycle Grade 3 nonhematologic toxicity, Grade 4 neutropenia lasting more than 7 days or Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with hemorrhage. Patient missing everolimus or lapatinib for 7 days or more, due to drug related toxicities during the first cycle, was also considered DLT. |
| Objective Response Rate: | 17% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Lapatinib and everolimus are well tolerated at doses of 1,250 and 5 mg po daily, respectively. Stable disease more than and equal to 4 monthsPR was achieved in 13 of 78 patients (17 %). |